Molecular examination of bone marrow stromal cells and chondroitinase ABC-assisted acellular nerve allograft for peripheral nerve regeneration

Abstract

The present study aimed to evaluate the molecular mechanisms underlying combinatorial bone marrow stromal cell (BMSC) transplantation and chondroitinase ABC (Ch-ABC) therapy in a model of acellular nerve allograft (ANA) repair of the sciatic nerve gap in rats. Sprague Dawley rats (n=24) were used as nerve donors and Wistar rats (n=48) were randomly divided into the following groups: Group I, Dulbecco's modified Eagle's medium (DMEM) control group (ANA treated with DMEM only); Group II, Ch-ABC group (ANA treated with Ch-ABC only); Group III, BMSC group (ANA seeded with BMSCs only); Group IV, Ch-ABC + BMSCs group (Ch-ABC treated ANA then seeded with BMSCs). After 8 weeks, the expression of nerve growth factor, brain-derived neurotrophic factor and vascular endothelial growth factor in the regenerated tissues were detected by reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Axonal regeneration, motor neuron protection and functional recovery were examined by immunohistochemistry, horseradish peroxidase retrograde neural tracing and electrophysiological and tibialis anterior muscle recovery analyses. It was observed that combination therapy enhances the growth response of the donor nerve locally as well as distally, at the level of the spinal cord motoneuron and the target muscle organ. This phenomenon is likely due to the propagation of retrograde and anterograde transport of growth signals sourced from the graft site. Collectively, growth improvement on the donor nerve, target muscle and motoneuron ultimately contribute to efficacious axonal regeneration and functional recovery. Thorough investigation of molecular peripheral nerve injury combinatorial strategies are required for the optimization of efficacious therapy and full functional recovery following ANA.

The combined effect of granulocyte-colony stimulating factor (G-CSF) treatment and exercise in rats with spinal cord injury

“…28 However, we found lower VEGF levels than those in the G-CSF or exercise groups, which differed from the results of a previous study. 29 we could explain our findings as G-CSF promotes angiogenesis first and stimulates neurogenesis later. Thus, neurogenesis was more critical than angiogenesis for motor function recovery, and combined treatment was more effective for motor function recovery because neurogenesis progressed faster than individual treatment.…”

The Effects of Epidermal Neural Crest Stem Cells on Local Inflammation Microenvironment in the Defected Sciatic Nerve of Rats

“…As the development of tissue engineering, the biodegradable artificial nerve is an alternative to autologous nerve grafts and used to bridge the stumps of defected peripheral nerve. Poly lactic co-glycolic acid (PLGA) nerve conduit can be combined with different donor cells, such as neural stem cells (NSCs; Omi et al, 2016 ), bone marrow stromal cells (BMSCs; Ying et al, 2016 ), shwann cells (SCs; You et al, 2011 ), olfactory ensheathing cells (OECs; Guerout et al, 2014 ), epidermal neural crest stem cells (EPI-NCSCs; Zhang et al, 2014 ), to provide a favorable microenvironment for preventing infiltration of scar tissue and guiding axonal regeneration (Li B. C. et al, 2010 ).…”

Synergistic effects of G‐CSF and bone marrow stromal cells on nerve regeneration with acellular nerve xenografts

“…Thus, BMSCs are preferred seed cells for use in constructing tissue‐engineered nerve transplants. An increasing number of in vivo studies have confirmed preferable therapeutic effects of BMSCs on neural regeneration (Wang et al, , Zarbakhsh, Goudarzi, Shirmohammadi, & Safari, ).…”

“…Bone marrow stromal cells (BMSCs) are attractive adult stem cells, since they possess merits such as easy accessibility, rapid proliferation, persistent survival and immunological compatibility; in addition, these cells are capable of undergoing multi‐directional differentiation and secreting of neurotrophic factors (Ide and Kanekiyo, ; Yang et al, ; Zheng et al, ). BMSCs have been utilized to repair central and peripheral neural injuries to some extent (Cuevas, Carceller, Garcia‐Gomez, Yan, & Dujovny, ; Hokari et al, ; Polisetti, Chaitanya, Babu, & Vemuganti, ; Wang et al, ).…”